The effects of human liver epoxide hydrolase were examined by using 3H(-)t-7,8-diol BP as a substrate to generate diol epoxide I and II in the incubation medium, with uninduced and BA-preinduced human monocytes, lymphocytes, Fischer rat liver (TRL-2) cells, and Buffalo rat liver (BRL) cells. The binding of reactive metabolites to added and intact cellular DNA was determined. The epoxide hydrolase was added either to incubation mixtures or to tissue culture media and inhibition of DNA binding was observed. In the second part of the project, major forms of cytochrome P-450 were purified from 3-methylcholanthrene (3MC), phenobarbital (PB), and Beta-naphtho-flavone (BNF)-treated rat liver microsomes. A purified, reconstituted microsomal mixed function oxidase (MFO) system, containing different forms of cytochrome P-450, NADPH cytochrome c (P-450), reductase and dilauroylglyceryl 3-phosphocholine was used to analyze benzo(a)pyrene metabolism. Each cytochrome P-450 exhibited a unique pattern of metabolism.